JP2007502430A - Equipment for polymerase chain reaction - Google Patents

Equipment for polymerase chain reaction Download PDF

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JP2007502430A
JP2007502430A JP2006532510A JP2006532510A JP2007502430A JP 2007502430 A JP2007502430 A JP 2007502430A JP 2006532510 A JP2006532510 A JP 2006532510A JP 2006532510 A JP2006532510 A JP 2006532510A JP 2007502430 A JP2007502430 A JP 2007502430A
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detection device
chamber
housing
heating element
sample
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JP4764341B2 (en
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ジェイソン グリーン，ダグラス
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スミス ディテクション インコーポレーテッド
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • B01L2300/1844—Means for temperature control using fluid heat transfer medium using fans
    • G01N2015/019—
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)

Abstract

検出装置は、試料を受容するように構成されたチャンバを収容する筺体と、チャンバ内に配置された加熱素子と、チャンバの観察を可能にする光学窓とを含む。筺体は、チャンバ中に流体を流動させ、それによって冷却を達成するように構成された通路を含む。  The detection device includes a housing that houses a chamber configured to receive a sample, a heating element disposed within the chamber, and an optical window that allows observation of the chamber. The enclosure includes a passage configured to flow fluid into the chamber and thereby achieve cooling.

Description

本願は、２００３年５月２８日に出願した米国特許仮出願第６０／４７３，４４７号の優先権および利益を主張し、それを参照によってここに組み込む。本発明は、ポリメラーゼ連鎖反応（ＰＣＲ）のための装置に関し、さらに詳しくは、ＰＣＲ技術を使用してサンプル中の生物剤の有無を検出するために手持ち式計器と共に使用することのできる装置に関する。   This application claims priority and benefit of US Provisional Application No. 60 / 473,447, filed May 28, 2003, which is hereby incorporated by reference. The present invention relates to an apparatus for polymerase chain reaction (PCR), and more particularly to an apparatus that can be used with a hand-held instrument to detect the presence or absence of a biological agent in a sample using PCR technology.

ＰＣＲ技術は、施設セキュリティ専門家、軍隊、および救急対応要員、例えば消防士、警察、緊急医療要員、および危険物処理班によって使用され、生命を脅かす生体有害物質が現場に存在するか否かを現地及び野外で決定することができる。例えば、ＰＣＲ技術を利用する生物学的検出計器は、炭疸菌のような生物剤が存在しないかを調べるサンプルを検査するために使用することができ、４０分またはそれ以下で正確な結果をもたらす。   PCR technology is used by facility security professionals, military and emergency response personnel, such as firefighters, police, emergency medical personnel, and hazardous materials teams, to determine whether life-threatening biohazardous materials are present in the field. It can be determined locally and outdoors. For example, a biological detection instrument that utilizes PCR technology can be used to test a sample for the presence of biological agents such as Bacillus anthracis, giving accurate results in 40 minutes or less. Bring.

サンプルは最初に、使い捨て反応管内でＰＣＲ反応混合物へと調剤される。反応管は、計器の反応装置内のチャンバ内へ挿置される。反応装置内で、反応混合物は熱サイクル（加熱および冷却）を受ける。生物剤の有無は計器によって光学的に検出される。   The sample is first dispensed into a PCR reaction mixture in a disposable reaction tube. The reaction tube is inserted into a chamber in the instrument's reactor. Within the reactor, the reaction mixture undergoes a thermal cycle (heating and cooling). The presence or absence of a biological agent is optically detected by a meter.

従来の反応装置の一つの不利点は、そのような反応装置が、現地及び野外で使用するのに適した携帯用（手持ち式）生物学的検出計器にパッケージ化するには重すぎ、かつ複雑すぎることである。例えば、従来の反応装置は、反応混合物を加熱および冷却するために加熱および冷却流体がその中を流れる金属ブロックから構成される（例えば、参照によって本書に組み込まれる米国特許第５，５５５，６７５号を参照されたい）。該金属ブロックならびに流体の温度および供給を制御するために必要な構成部品は、反応装置の重量および複雑さを増大する。その結果、生物学的検出計器の重量および複雑さが増大するので、計器を容易に現地および野外の現場に運ぶことができない。   One disadvantage of conventional reactors is that such reactors are too heavy and complex to package into portable (handheld) biological detection instruments suitable for field and field use. Too much. For example, a conventional reactor consists of a metal block through which heating and cooling fluid flows to heat and cool the reaction mixture (eg, US Pat. No. 5,555,675, incorporated herein by reference). See). The metal block and the components necessary to control fluid temperature and supply increase the weight and complexity of the reactor. As a result, the weight and complexity of biological detection instruments increases and the instrument cannot be easily transported to the field and field sites.

従来の反応装置の別の不利点は、そのような反応装置が反応混合物を急速または効率的に加熱および冷却できないことである。例えば、従来の反応装置の金属ブロックは高い熱伝導率を有するので、熱は反応混合物から金属ブロックを通して計器内に逆に伝達される。したがって、反応装置の加熱効率が低減する。その結果、熱サイクルを完了するための時間が増大する。   Another disadvantage of conventional reactors is that such reactors cannot heat and cool the reaction mixture rapidly or efficiently. For example, since the metal block of a conventional reactor has a high thermal conductivity, heat is transferred back from the reaction mixture through the metal block and into the instrument. Therefore, the heating efficiency of the reactor is reduced. As a result, the time to complete the thermal cycle is increased.

一部の従来の反応装置は、反応混合物を急速に加熱および冷却するために、発熱素子を一体化した微細加工シリコンを使用しているが、そのような反応装置は比較的高い工具費、労賃、および生産コストが悩みである（例えば、参照によって本書に組み込まれる米国特許第５，５８９，１３６号を参照されたい）。さらに、微細加工された発熱体の脆弱性は、そのような発熱体を携帯野外用としては非現実的にする。   Some conventional reactors use microfabricated silicon with integrated heating elements to rapidly heat and cool the reaction mixture, but such reactors have relatively high tool costs, labor costs. And production costs (see, for example, US Pat. No. 5,589,136, incorporated herein by reference). Further, the vulnerability of the microfabricated heating element makes such a heating element impractical for portable outdoor use.

本発明の一態様では、検出装置を提供する。該検出装置は、試料を受容するように構成されたチャンバを収容する筺体と、該チャンバ内に配置された加熱素子と、該チャンバの観察を可能にする光学窓とを含む。筺体は、流体をチャンバ中に流動させ、それによって冷却を達成するように構成された通路を含む。   In one embodiment of the present invention, a detection device is provided. The detection device includes a housing that houses a chamber configured to receive a sample, a heating element disposed within the chamber, and an optical window that allows observation of the chamber. The enclosure includes a passage configured to cause fluid to flow into the chamber and thereby achieve cooling.

本発明の別の態様では、生物剤を検出するための計器を提供する。該計器はアレイ状に配設された複数の筺体を含む。各筺体は、試料を受容するように構成されたチャンバと、該チャンバ内に配置された加熱素子と、該チャンバの観察を可能にする光学窓とを含む。加えて、各筺体は、流体をチャンバ中に流動させ、それによって冷却を達成するように構成された通路を含む。   In another aspect of the invention, an instrument for detecting a biological agent is provided. The instrument includes a plurality of housings arranged in an array. Each housing includes a chamber configured to receive a sample, a heating element disposed within the chamber, and an optical window that allows observation of the chamber. In addition, each housing includes a passage configured to flow fluid into the chamber, thereby achieving cooling.

この明細書に組み込まれ、その一部を構成する添付の図面は、本発明の実施形態を示し、解説と共に本発明の原理を説明するのに役立つ。   The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.

図１を参照すると、計器４０用の検出装置１は一般的に、筺体１０、加熱素子２０、および光学アパーチャ(optical aperture)（窓：window）３０を含む。   Referring to FIG. 1, a detection device 1 for an instrument 40 generally includes a housing 10, a heating element 20, and an optical aperture (window) 30.

筺体１０は、炭疸菌、野兎病、疫病、または天然痘のような生物剤を潜在的に含む試料（サンプル）を受容するように構成される。試料は、筺体１０内に挿置することのできる長尺部分を有する使い捨て反応管内に収容することができる。参照によって本書に組み込む、２００３年１２月４日に出願された米国特許出願第１０／７３７，０３７号、および２００３年５月２８日に出願された米国特許仮出願第６０／４７３，５３９号に記載されているように、反応チャンバ１は反応管（サンプル保持器）と共に使用することが好ましい。   The rod 10 is configured to receive a sample (sample) potentially containing a biological agent such as anthrax, wild boar, plague, or smallpox. The sample can be stored in a disposable reaction tube having a long portion that can be inserted into the housing 10. In US patent application Ser. No. 10 / 737,037 filed on Dec. 4, 2003 and U.S. Provisional Application No. 60 / 473,539 filed on May 28, 2003, which are incorporated herein by reference. As described, the reaction chamber 1 is preferably used with a reaction tube (sample holder).

図１に示すように、筺体１０は筺体１０の高さＨが筺体１０の幅Ｗより大きくなるように形作ることができる。高さＨを筺体１０の奥行きＤより大きくすることもできる。したがって、筺体１０は矩形の形状を有する。筺体１０の底部は、計器４０の装着用レール内への筺体１０の挿入を容易にするために、一対の脚１７を含む。   As shown in FIG. 1, the housing 10 can be shaped such that the height H of the housing 10 is greater than the width W of the housing 10. The height H can be made larger than the depth D of the housing 10. Therefore, the housing 10 has a rectangular shape. The bottom of the housing 10 includes a pair of legs 17 to facilitate insertion of the housing 10 into the instrument 40 mounting rail.

筺体１０は、試料を受容するように構成されたチャンバ１２を形成するために、一つに結合される第一部分１０ａ（図３に示す）および第二部分１０ｂを含む。第二部分１０ｂは構造的に第一部分１０ａと同様であり（第二部分１０ｂに光学アパーチャ３０が欠如していることを除く）、第一部分１０ａと嵌合するように構成される。第一部分１０ａおよび第二部分１０ｂは、いずれかの従来の方法で（例えば接着剤を使用して）一つに結合することができるが、パチンと嵌め合う(snap together)ように構成することが好ましい。例えば、第一部分１０ａおよび第二部分１０ｂは各々、筺体１０の他方の部分１０ａまたは１０ｂに配置された対応するアパーチャ(aperture)１４ｂ内にパチンと嵌って係合するように構成された、一つまたはそれ以上のタング１４ａ（図４および５に示す）を含むことができる。   The housing 10 includes a first portion 10a (shown in FIG. 3) and a second portion 10b that are joined together to form a chamber 12 that is configured to receive a sample. The second portion 10b is structurally similar to the first portion 10a (except that the second portion 10b lacks the optical aperture 30) and is configured to mate with the first portion 10a. The first portion 10a and the second portion 10b can be joined together in any conventional manner (eg, using an adhesive), but can be configured to snap together. preferable. For example, each of the first portion 10a and the second portion 10b is configured to snap into and engage within a corresponding aperture 14b disposed in the other portion 10a or 10b of the housing 10. Or more tongues 14a (shown in FIGS. 4 and 5) can be included.

筺体１０はまた、流体がチャンバ１２中を流動して冷却を達成することができるように構成された、通路１６をも含む。例えば通路１６は、図１に示すように上下に配置された複数の溝(channel)１６ａを含むことができる。各溝１６ａは、筺体１０の第一側面から筺体１０の第二側面まで延在することが好ましい。したがって、溝１６ａは筺体１０中全体に延在する（図４に示す通り）。加えて、試料がチャンバ１２内に受容されたときに、流体が試料を超えて流動するように、溝１６ａはチャンバ１２と交差する。この方法により、空気のような流体はチャンバ１２中を流動し、それによって熱を除去し、試料に冷却をもたらすことができる。   The enclosure 10 also includes a passage 16 configured to allow fluid to flow through the chamber 12 to achieve cooling. For example, the passage 16 may include a plurality of channels 16a arranged one above the other as shown in FIG. Each groove 16 a preferably extends from the first side surface of the housing 10 to the second side surface of the housing 10. Therefore, the groove 16a extends throughout the housing 10 (as shown in FIG. 4). In addition, the groove 16a intersects the chamber 12 so that fluid flows past the sample when the sample is received in the chamber 12. By this method, a fluid such as air can flow through the chamber 12, thereby removing heat and providing cooling to the sample.

本発明の一実施形態では、筺体１０は電気絶縁性材料から作られる。該材料は例えばプラスチック、ポリマ、または樹脂とすることができ、約１Ｗ／ｍ−Ｋ未満の熱伝導度を持つことができる。筺体１０は、商品名ＶＡＬＯＸ（登録商標）によって知られる樹脂のような熱可塑性ポリエステル樹脂から形成することが好ましい。本発明の別の実施形態では、筺体１０は断熱性材料から形成される。その結果、加熱素子２０は筺体１０によって計器４０から断熱されるので、筺体１０を通して計器４０へ伝達される熱の量がかなり低減される。したがって、加熱素子２０によって発生する熱が試料に集中する。筺体１０は、電気的絶縁性および断熱性の両方である材料から形成することが好ましい。ＶＡＬＯＸ（登録商標）は模範的材料である。プラスチック、ポリマ、または樹脂材を使用して筺体１０を形成することにより、金属ブロックから作られた従来の装置の重量に対して、筺体１０の重量が低減される。その結果、検出装置１は改善された熱効率、より低いコストを有し、携帯性が高まり、かつ取り扱いが容易になる。   In one embodiment of the invention, the housing 10 is made from an electrically insulating material. The material can be, for example, a plastic, polymer, or resin and can have a thermal conductivity of less than about 1 W / m-K. The housing 10 is preferably formed from a thermoplastic polyester resin such as a resin known by the trade name VALOX (registered trademark). In another embodiment of the present invention, the housing 10 is formed from a heat insulating material. As a result, the heating element 20 is insulated from the instrument 40 by the enclosure 10 so that the amount of heat transferred through the enclosure 10 to the instrument 40 is significantly reduced. Therefore, the heat generated by the heating element 20 is concentrated on the sample. The housing 10 is preferably formed from a material that is both electrically insulating and thermally insulating. VALOX® is an exemplary material. Forming the housing 10 using plastic, polymer, or resin material reduces the weight of the housing 10 relative to the weight of conventional devices made from metal blocks. As a result, the detection device 1 has improved thermal efficiency, lower cost, increased portability, and ease of handling.

試料がチャンバ１２内に挿置されたときに、試料の温度を高めることができるように、加熱素子２０はチャンバ１２に熱を提供する。加熱素子２０は可撓性とすることができ、かつ例えば約０．０１５インチ以下の厚さを持つことができる。模範的実施形態では、加熱素子２０は、基板２１上に堆積された二つのエッチング抵抗素子(etched resistance element)２２（発熱体）を含む薄膜抵抗体である。基板２１はポリエステル膜、例えば商品名ＭＹＬＡＲ（登録商標）によって知られるポリエステル膜、またはポリイミド膜、例えば商品名ＫＡＰＴＯＮ（登録商標）によって知られるポリイミド膜とすることができる。加熱素子２０はまた、加熱素子２０の温度を感知するためのサーミスタ２３をも含むことができる。   The heating element 20 provides heat to the chamber 12 so that the temperature of the sample can be increased when the sample is inserted into the chamber 12. The heating element 20 can be flexible and can have a thickness of, for example, about 0.015 inches or less. In the exemplary embodiment, the heating element 20 is a thin film resistor that includes two etched resistance elements 22 (heating elements) deposited on a substrate 21. The substrate 21 may be a polyester film, for example a polyester film known by the trade name MYLAR®, or a polyimide film, for example a polyimide film known by the trade name KAPTON®. The heating element 20 can also include a thermistor 23 for sensing the temperature of the heating element 20.

加熱素子２０（図２に示す）は、チャンバ１２内でチャンバ１２の壁上に配置するように構成される。加熱素子２０は例えば、接着剤を使用してチャンバ１２の壁に接着することができる。模範的実施形態では、加熱素子２０は、筺体の第一部分１０ａおよび第二部分１０ｂが嵌合される前に、筺体１０に取り付けられる単一組立体である。この実施形態では、加熱素子２０の一端２０ａが筺体の第一部分１０ａに取り付けられ、加熱素子２０の他端２０ｂが筺体の第二部分１０ｂに取り付けられる。加熱素子２０の中心部分２０ｃは折れ曲がるように構成されるので、次いで筺体１０の第一および第二部分１０ａ、１０ｂを結合することができる。このようにして、加熱素子２０は筺体１０のチャンバ１２内に設置される。   The heating element 20 (shown in FIG. 2) is configured to be disposed within the chamber 12 on the wall of the chamber 12. The heating element 20 can be adhered to the wall of the chamber 12 using, for example, an adhesive. In the exemplary embodiment, the heating element 20 is a single assembly that is attached to the housing 10 before the first and second portions 10a and 10b of the housing are mated. In this embodiment, one end 20a of the heating element 20 is attached to the first portion 10a of the housing, and the other end 20b of the heating element 20 is attached to the second portion 10b of the housing. Since the central portion 20c of the heating element 20 is configured to be bent, the first and second portions 10a, 10b of the housing 10 can then be joined. In this way, the heating element 20 is installed in the chamber 12 of the housing 10.

加熱素子２０は、計器４０内の電源に接続されるように構成される。例えば加熱素子２０は、抵抗素子２２用のリード線２４ａおよびサーミスタ２３用のリード線２４ｂを含むことができる。各々のリード線２４ａ、２４ｂの一端は加熱素子２０に圧着または接着することができ、各々のリード線２４ａ、２４ｂの他端は、電源に接続するためのコネクタ２６（例えばワイヤ対ワイヤレセプタクル）で終端することができる。加熱素子２０は追加的に、光学アパーチャ３０の一部を構成する開口２８を含むことができる。   The heating element 20 is configured to be connected to a power source in the meter 40. For example, the heating element 20 can include a lead 24 a for the resistance element 22 and a lead 24 b for the thermistor 23. One end of each lead wire 24a, 24b can be crimped or bonded to the heating element 20, and the other end of each lead wire 24a, 24b is a connector 26 (eg, a wire-to-wire receptacle) for connection to a power source. Can be terminated. The heating element 20 can additionally include an opening 28 that forms part of the optical aperture 30.

光学アパーチャ３０は、計器４０によるチャンバ１２の光学的監視または観察を可能にするように構成される。図１および４に示すように、光学アパーチャ３０は、筺体１０の壁を貫通して延びる第一開口３２ａおよび第二開口３２ｂを含む。開口３２ａおよび３２ｂは例えば、第一開口３２ａが第二開口３２ｂの上に配置されるように、上下に配置することができる。加熱素子２０が筺体１０内に設置されるときに、光学アパーチャ３０が加熱素子２０を貫通して延びるように、加熱素子の開口２８は開口３２ａおよび３２ｂと位置合わせされる。したがって、加熱素子２０は光学アパーチャ３０のチャンバ１２内への視線経路を遮断しない。   The optical aperture 30 is configured to allow the instrument 40 to optically monitor or observe the chamber 12. As shown in FIGS. 1 and 4, the optical aperture 30 includes a first opening 32 a and a second opening 32 b that extend through the wall of the housing 10. The openings 32a and 32b can be arranged up and down, for example, such that the first opening 32a is arranged above the second opening 32b. When the heating element 20 is installed in the housing 10, the opening 28 of the heating element is aligned with the openings 32a and 32b so that the optical aperture 30 extends through the heating element 20. Accordingly, the heating element 20 does not block the line-of-sight path into the chamber 12 of the optical aperture 30.

光学アパーチャ３０は、試料が検出装置１のチャンバ１２内に挿置されたときに、計器４０内の検出器が試料を分析することができるように構成される。検出器は、光学分光分析を使用して、生物剤が試料中に存在するかどうかを決定する。検出器はいずれかの適切な検出器とすることができるが、蛍光に基づく光学分光分析を使用する検出器であることが好ましい。操作時に、使用者はサンプルを使い捨て反応管内でＰＣＲ反応混合物へと調剤し、反応管を検出装置１のチャンバ１２内へ挿置する。検出装置１で、反応混合物を一連の熱サイクル（例えば４０〜５０回の熱サイクル）にさらすことによって、ＤＮＡ増幅が達成される。模範的実施形態では、各熱サイクル中に検出装置１は、加熱素子２０を起動させることによって、反応混合物を摂氏約９６度の温度まで加熱し、次いで加熱素子２０の動作を停止し、空気を溝１６ａに流動させることによって、反応混合物の温度を摂氏約６０度の温度まで冷却する。空気流は、ファンのような空気源によって付勢される強制空気流であることが好ましい。熱サイクルが完了すると、励起波長が開口３２ａ、３２ｂの一つを通って向けられ、検出（発光）波長が開口３２ａ、３２ｂのもう一つを通って向けられ、それによって生物剤が反応混合物内に存在するかどうかが決定される。蛍光発光の増加は、生物剤の存在に関連付けられる。   The optical aperture 30 is configured such that the detector in the instrument 40 can analyze the sample when the sample is inserted into the chamber 12 of the detection device 1. The detector uses optical spectroscopy to determine whether a biological agent is present in the sample. The detector can be any suitable detector, but is preferably a detector that uses fluorescence-based optical spectroscopy. In operation, the user dispenses the sample into a PCR reaction mixture in a disposable reaction tube and inserts the reaction tube into the chamber 12 of the detector 1. With the detection device 1, DNA amplification is achieved by subjecting the reaction mixture to a series of thermal cycles (eg, 40-50 thermal cycles). In an exemplary embodiment, during each thermal cycle, the detection device 1 heats the reaction mixture to a temperature of about 96 degrees Celsius by activating the heating element 20 and then stops the operation of the heating element 20 to allow air to flow. The temperature of the reaction mixture is cooled to a temperature of about 60 degrees Celsius by flowing in the groove 16a. The air flow is preferably a forced air flow energized by an air source such as a fan. When the thermal cycle is complete, the excitation wavelength is directed through one of the openings 32a, 32b and the detection (emission) wavelength is directed through the other of the openings 32a, 32b, thereby allowing the biological agent to enter the reaction mixture. Whether it exists. The increase in fluorescence is associated with the presence of the biological agent.

検出装置１の上述した実施形態は、軽量で手持ち式の計器４０（図６に示す）と共に使用することができる。模範的実施形態では、計器４０は、複数のサンプルを同時に分析することができるように、図６に示すようにアレイ状に配設された、幾つかの独立して動作する検出装置１を含む。この方法により、生体有害物質を検出するためのＰＣＲ技術は、現地及び野外で施設セキュリティ専門家、軍隊、および救急対応要員に容易に利用可能になる。   The above-described embodiment of the detection device 1 can be used with a lightweight, hand-held instrument 40 (shown in FIG. 6). In the exemplary embodiment, instrument 40 includes a number of independently operating detection devices 1 arranged in an array as shown in FIG. 6 so that multiple samples can be analyzed simultaneously. . This method makes PCR technology for detecting biohazardous materials readily available to facility security professionals, the military, and emergency personnel in the field and outdoors.

したがって、上述した例示的実施形態では、ＰＣＲ技術を使用してサンプル中の生物剤の有無を検出するために手持ち式計器と共に使用することのできる装置がもたらされる。   Thus, the exemplary embodiments described above provide an apparatus that can be used with a handheld instrument to detect the presence or absence of a biological agent in a sample using PCR technology.

本発明の変形および他の実施形態は、本書に開示した本発明の詳細および実施の検討から、当業者には明白であろう。詳細および実施例は単なる例示とみなされ、発明の範囲は付属の請求の範囲によってのみ限定されることを意図している。   Variations and other embodiments of the invention will be apparent to those skilled in the art from consideration of the details and practice of the invention disclosed herein. The details and examples are to be considered merely exemplary and the scope of the invention is intended to be limited only by the scope of the appended claims.

本発明に係る検出装置の実施形態の斜視図である。1 is a perspective view of an embodiment of a detection device according to the present invention. 図１の検出装置の加熱要素の上面図である。FIG. 2 is a top view of a heating element of the detection device of FIG. 図１の検出装置の第一部分の立面図である。FIG. 2 is an elevational view of a first portion of the detection device of FIG. 1. 図３の線Ａ−Ａに沿って切った断面図である。FIG. 4 is a cross-sectional view taken along line AA in FIG. 3. 図１の検出装置の第一部分の上面図である。It is a top view of the 1st part of the detection apparatus of FIG. 本発明に係る携帯検出計器の実施形態の斜視図である。It is a perspective view of the embodiment of the portable detection instrument concerning the present invention.

符号の説明Explanation of symbols

１ 検出装置
１０ 筐体
２０ 加熱素子
３０ 光学アパーチャ
４０ 計器

DESCRIPTION OF SYMBOLS 1 Detection apparatus 10 Case 20 Heating element 30 Optical aperture 40 Instrument

Claims (32)

試料を受容するように構成されたチャンバを収容する筺体と、前記チャンバ内に配置された加熱素子と、前記チャンバの観察を可能にする光学窓とを備えた検出装置であって、前記チャンバ中に流体を流動させそれによって冷却を達成するように構成された通路が前記筺体に含まれる検出装置。   A detection device comprising a housing containing a chamber configured to receive a sample, a heating element disposed in the chamber, and an optical window allowing observation of the chamber, A detection device, wherein the housing includes a passage configured to cause fluid to flow therethrough and thereby achieve cooling. 前記筺体が断熱材を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the casing includes a heat insulating material. 前記筺体が電気絶縁体を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the housing includes an electrical insulator. 前記筺体がプラスチックを含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the housing includes plastic. 前記筺体がポリマ材料を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the housing includes a polymer material. 前記筺体が樹脂を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the housing includes a resin. 前記樹脂が熱可塑性ポリエステル樹脂を含む、請求項６に記載の検出装置。   The detection device according to claim 6, wherein the resin includes a thermoplastic polyester resin. 前記筺体が約１Ｗ／ｍ−Ｋ未満の熱伝導度を有する材料を含む、請求項１に記載の検出装置。   The detection device of claim 1, wherein the housing includes a material having a thermal conductivity of less than about 1 W / m-K. 前記筺体の高さが前記筺体の幅より大きく、かつ前記筺体の奥行きより大きい、請求項１に記載の検出装置。   The detection device according to claim 1, wherein a height of the housing is larger than a width of the housing and larger than a depth of the housing. 前記筺体が、一つに結合されてチャンバを形成する第一部分および第二部分を含む、請求項１に記載の検出装置。   The detection device of claim 1, wherein the housing includes a first portion and a second portion that are joined together to form a chamber. 前記第一部分および前記第二部分がパチンと嵌め合うように構成された、請求項１０に記載の検出装置。   The detection device according to claim 10, wherein the first portion and the second portion are configured to fit into a snap. 前記第一部分が突起を含み、前記第二部分がアパーチャを含み、前記突起および前記アパーチャが係合して、前記第一部分および前記第二部分がパチンと嵌め合うことができるように構成された、請求項１１に記載の検出装置。   The first portion includes a protrusion, the second portion includes an aperture, and the protrusion and the aperture are engaged with each other, and the first portion and the second portion can be snapped into engagement with each other. The detection device according to claim 11. 前記加熱素子が薄膜抵抗体を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the heating element includes a thin film resistor. 前記薄膜抵抗体が、基板上に配置されたエッチング抵抗素子を含む、請求項１３に記載の検出装置。   The detection apparatus according to claim 13, wherein the thin film resistor includes an etching resistance element disposed on a substrate. 前記基板がポリエステル膜を含む、請求項１４に記載の検出装置。   The detection device according to claim 14, wherein the substrate includes a polyester film. 前記基板がポリイミド膜を含む、請求項１４に記載の検出装置。   The detection device according to claim 14, wherein the substrate includes a polyimide film. 前記加熱素子が可撓性である、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the heating element is flexible. 前記加熱素子が第一発熱体および第二発熱体を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the heating element includes a first heating element and a second heating element. 前記第一発熱体が前記チャンバの第一壁上に配置され、かつ前記第二発熱体が前記チャンバの前記第一壁に対向する第二壁上に配置された、請求項１８に記載の検出装置。   19. Detection according to claim 18, wherein the first heating element is disposed on a first wall of the chamber and the second heating element is disposed on a second wall opposite the first wall of the chamber. apparatus. 前記流体が空気を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the fluid includes air. 前記通路が上下に配置された複数の溝を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the passage includes a plurality of grooves arranged vertically. 前記通路が前記筺体の第一側面から前記筺体の第二側面まで延在する請求項１に記載の検出装置。   The detection device according to claim 1, wherein the passage extends from a first side surface of the housing to a second side surface of the housing. 前記光学窓は、前記検出装置による前記チャンバの光学的監視を可能にするように構成される、請求項１に記載の検出装置。   The detection device of claim 1, wherein the optical window is configured to allow optical monitoring of the chamber by the detection device. 前記光学窓は、前記筺体の壁を貫通して延びる開口を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the optical window includes an opening extending through the wall of the housing. 前記光学窓は、前記加熱素子を貫通して延びる開口を含む、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the optical window includes an opening extending through the heating element. 前記開口が第一開口と、前記第一開口の下に配置された第二開口とを含む、請求項２４に記載の検出装置。   The detection device according to claim 24, wherein the opening includes a first opening and a second opening disposed below the first opening. 前記検出装置が試料の蛍光を検出するように構成された、請求項１に記載の検出装置。   The detection device according to claim 1, wherein the detection device is configured to detect fluorescence of a sample. 前記試料が反応管内に収容される、請求項１に記載の検出装置。   The detection apparatus according to claim 1, wherein the sample is accommodated in a reaction tube. 前記反応管が、前記チャンバに受容されるように構成された、請求項２８に記載の検出装置。   30. The detection device of claim 28, wherein the reaction tube is configured to be received in the chamber. 生物剤を検出するための携帯計器であって、
アレイ状に配設された複数の筺体
を備え、
各筺体は、試料を受容するように構成されたチャンバと、前記チャンバ内に配置された加熱素子と、前記チャンバの観察を可能にする光学窓とを含み、かつ
各筺体は、流体を前記チャンバ中に流動させそれによって冷却を達成するように構成された通路を含む、
携帯計器。 A portable instrument for detecting biological agents,
Provided with a plurality of housings arranged in an array,
Each enclosure includes a chamber configured to receive a sample, a heating element disposed within the chamber, and an optical window that allows observation of the chamber, and each enclosure provides fluid to the chamber Including a passage configured to flow into and thereby achieve cooling,
Portable instrument. 前記携帯計器が使用者の手の中に保持されるように構成された、請求項２９に記載の携帯検出装置。   30. The portable detection device of claim 29, wherein the portable instrument is configured to be held in a user's hand. 前記携帯計器が六個の筺体を含む、請求項２９に記載の携帯検出装置。   30. The portable detection device according to claim 29, wherein the portable meter includes six housings.
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US9861570B2 (en) 2008-09-02 2018-01-09 Allergan Holdings France S.A.S. Threads of hyaluronic acid and/or derivatives thereof, methods of making thereof and uses thereof
US11154484B2 (en) 2008-09-02 2021-10-26 Allergan Holdings France S.A.S. Threads of hyaluronic acid and/or derivatives thereof, methods of making thereof and uses thereof

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US20050002024A1 (en) 2005-01-06
JP4764341B2 (en) 2011-08-31
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WO2005009617A1 (en) 2005-02-03
EP1631387B1 (en) 2013-06-26

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